The goal of this research is to study the function and regulation of a novel kinase S6K2. S6K2 was recently cloned based on its homology to a well- known S6K1. Cancer research on molecular processes involved in cell division identified S6K1 as possibly playing an important role. S6K1 was especially routed as the key to cellular proliferation when it was discovered that the immunosuppressant drug rapamycin might exert its anti-proliferative effects through S6K1. However, rapamycin was subsequently shown to have other cellular targets besides S6K1, and identifying other S6K1-like molecules became important in understanding cellular proliferation. S6K2 is one such protein. Much of its biological role as well as its kinase activity regulation are unknown at this time, and further research is necessary in order to better understand its role in cellular function. There are four objectives in this research proposal. The first objective is to analyze regulation of S6K2 activity will be studied. Next is to study the functional similarities and differences between S6K1 and S6K2. Although S6K1 and S6K2 have some sequence similarities, there are also many differences between the two. The hypothesis is that the two kinases have different cellular functions. The third objective is to understand the role of S6K2 in the function of the immune system using various cellular, biochemical and molecular methods. Preliminary data indicate that S6K2 may be an important kinase in immune cell functions. The last objective is to analyze proteins that associate with the and C-terminal regions of S6K2. Analyzing S6K2-associating proteins would be informative in learning about the function of S6K2.